ICU-acquired weakness Vanhorebeek, Ilse; Latronico, Nicola; Van den Berghe, Greet
Intensive care medicine,
04/2020, Letnik:
46, Številka:
4
Journal Article
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Critically ill patients often acquire neuropathy and/or myopathy labeled ICU-acquired weakness. The current insights into incidence, pathophysiology, diagnostic tools, risk factors, short- and ...long-term consequences and management of ICU-acquired weakness are narratively reviewed. PubMed was searched for combinations of “neuropathy”, “myopathy”, “neuromyopathy”, or “weakness” with “critical illness”, “critically ill”, “ICU”, “PICU”, “sepsis” or “burn”. ICU-acquired weakness affects limb and respiratory muscles with a widely varying prevalence depending on the study population. Pathophysiology remains incompletely understood but comprises complex structural/functional alterations within myofibers and neurons. Clinical and electrophysiological tools are used for diagnosis, each with advantages and limitations. Risk factors include age, weight, comorbidities, illness severity, organ failure, exposure to drugs negatively affecting myofibers and neurons, immobility and other intensive care-related factors. ICU-acquired weakness increases risk of in-ICU, in-hospital and long-term mortality, duration of mechanical ventilation and of hospitalization and augments healthcare-related costs, increases likelihood of prolonged care in rehabilitation centers and reduces physical function and quality of life in the long term. RCTs have shown preventive impact of avoiding hyperglycemia, of omitting early parenteral nutrition use and of minimizing sedation. Results of studies investigating the impact of early mobilization, neuromuscular electrical stimulation and of pharmacological interventions were inconsistent, with recent systematic reviews/meta-analyses revealing no or only low-quality evidence for benefit. ICU-acquired weakness predisposes to adverse short- and long-term outcomes. Only a few preventive, but no therapeutic, strategies exist. Further mechanistic research is needed to identify new targets for interventions to be tested in adequately powered RCTs.
Studies indicate that mechanically ventilated patients develop significant diaphragm muscle weakness, but the etiology of weakness and its clinical impact remain incompletely understood. We assessed ...diaphragm strength in mechanically ventilated medical ICU patients, correlated the development of diaphragm weakness with multiple clinical parameters, and examined the relationship between the level of diaphragm weakness and patient outcomes.
Transdiaphragmatic twitch pressure (PdiTw) in response to bilateral magnetic stimulation of the phrenic nerves was measured. Diaphragm weakness was correlated with the presence of infection, blood urea nitrogen, albumin, and glucose levels. The relationship of diaphragm strength to patient outcomes, including mortality and the duration of mechanical ventilation for successfully weaned patients, was also assessed.
We found that infection is a major risk factor for diaphragm weakness in mechanically ventilated medical ICU patients. Outcomes for patients with severe diaphragm weakness (PdiTw<10 cmH2O) were poor, with a markedly increased mortality (49%) compared to patients with PdiTw≥10 cmH2O (7% mortality, P=0.022). In addition, survivors with PdiTw<10 cmH2O required a significantly longer duration of mechanical ventilation (12.3±1.7 days) than those with PdiTw≥10 cmH2O (5.5±2.0 days, P=0.016).
Infection is a major cause of severe diaphragm weakness in mechanically ventilated patients. Moreover, diaphragm weakness is an important determinant of poor outcomes in this patient population.
BACKGROUND/OBJECTIVES
The extent to which the prevalence of muscle weakness in the US population varies by different putative grip strength constructs developed by the Sarcopenia Definitions and ...Outcomes Consortium (SDOC) has not been described.
DESIGN
Cross‐sectional analysis.
SETTING
Two nationally representative cohorts—2010 and 2012 waves of the Health and Retirement Survey and round 1 (2011) of the National Health and Aging Trends Survey.
PARTICIPANTS
Adults aged 65 years and older (n = 12,984) were included in these analyses.
MEASUREMENTS
We analyzed three constructs of muscle weakness developed by the SDOC, and found to be associated with mobility disability for men and women, respectively: absolute grip strength (<35.5 kg and 20 kg); grip strength standardized to body mass index (<1.05 kg/kg/m² and 0.79 kg/kg/m²); and grip strength standardized to weight (<0.45 kg/kg and 0.337 kg/kg). We estimated the prevalence of muscle weakness defined by each of these constructs in the overall older US population, and by age, sex, race, and ethnicity. We also estimated the sensitivity and specificity of each of the grip strength constructs to discriminate slowness (gait speed <0.8 m/s) in these samples.
RESULTS
The prevalence of muscle weakness ranged from 23% to 61% for men and from 30% to 66% for women, depending on the construct used. There was substantial variation in the prevalence of muscle weakness by race and ethnicity. The sensitivity and specificity of these measures for discriminating slowness varied widely, ranging from 0.30 to 0.92 (sensitivity) and from 0.17 to 0.88 (specificity).
CONCLUSIONS
The prevalence of muscle weakness, defined by the putative SDOC grip strength constructs, depends on the construct of weakness used. J Am Geriatr Soc 68:1438‐1444, 2020.
See related editorial by Cesari et al in this issue
Diaphragmatic function is a major determinant of the ability to successfully wean patients from mechanical ventilation (MV). Paradoxically, MV itself results in a rapid loss of diaphragmatic strength ...in animals. However, very little is known about the time course or mechanistic basis for such a phenomenon in humans.
To determine in a prospective fashion the time course for development of diaphragmatic weakness during MV; and the relationship between MV duration and diaphragmatic injury or atrophy, and the status of candidate cellular pathways implicated in these phenomena.
Airway occlusion pressure (TwPtr) generated by the diaphragm during phrenic nerve stimulation was measured in short-term (0.5 h; n = 6) and long-term (>5 d; n = 6) MV groups. Diaphragmatic biopsies obtained during thoracic surgery (MV for 2-3 h; n = 10) and from brain-dead organ donors (MV for 24-249 h; n = 15) were analyzed for ultrastructural injury, atrophy, and expression of proteolysis-related proteins (ubiquitin, nuclear factor-κB, and calpains).
TwPtr decreased progressively during MV, with a mean reduction of 32 ± 6% after 6 days. Longer periods of MV were associated with significantly greater ultrastructural fiber injury (26.2 ± 4.8 vs. 4.7 ± 0.6% area), decreased cross-sectional area of muscle fibers (1,904 ± 220 vs. 3,100 ± 329 μm²), an increase of ubiquitinated proteins (+19%), higher expression of p65 nuclear factor-κB (+77%), and greater levels of the calcium-activated proteases calpain-1, -2, and -3 (+104%, +432%, and +266%, respectively) in the diaphragm.
Diaphragmatic weakness, injury, and atrophy occur rapidly in critically ill patients during MV, and are significantly correlated with the duration of ventilator support.
Background
Skeletal muscle wasting and weakness are significant complications of critical illness, associated with degree of illness severity and periods of reduced mobility during mechanical ...ventilation. They contribute to the profound physical and functional deficits observed in survivors. These impairments may persist for many years following discharge from the intensive care unit (ICU) and can markedly influence health‐related quality of life. Rehabilitation is a key strategy in the recovery of patients after critical illness. Exercise‐based interventions are aimed at targeting this muscle wasting and weakness. Physical rehabilitation delivered during ICU admission has been systematically evaluated and shown to be beneficial. However, its effectiveness when initiated after ICU discharge has yet to be established.
Objectives
To assess the effectiveness of exercise rehabilitation programmes, initiated after ICU discharge, for functional exercise capacity and health‐related quality of life in adult ICU survivors who have been mechanically ventilated longer than 24 hours.
Search methods
We searched the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid SP MEDLINE, Ovid SP EMBASE and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) via EBSCO host to 15 May 2014. We used a specific search strategy for each database. This included synonyms for ICU and critical illness, exercise training and rehabilitation. We searched the reference lists of included studies and contacted primary authors to obtain further information regarding potentially eligible studies. We also searched major clinical trials registries (Clinical Trials and Current Controlled Trials) and the personal libraries of the review authors. We applied no language or publication restriction. We reran the search in February 2015 and will deal with the three studies of interest when we update the review.
Selection criteria
We included randomized controlled trials (RCTs), quasi‐RCTs and controlled clinical trials (CCTs) that compared an exercise intervention initiated after ICU discharge versus any other intervention or a control or ‘usual care’ programme in adult (≥ 18 years) survivors of critical illness.
Data collection and analysis
We used standard methodological procedures as expected by the Cochrane Collaboration.
Main results
We included six trials (483 adult ICU participants). Exercise‐based interventions were delivered on the ward in two studies; both on the ward and in the community in one study; and in the community in three studies. The duration of the intervention varied according to length of hospital stay following ICU discharge (up to a fixed duration of 12 weeks).
Risk of bias was variable for all domains across all trials. High risk of bias was evident in all studies for performance bias, although blinding of participants and personnel in therapeutic rehabilitation trials can be pragmatically challenging. For other domains, at least half of the studies were at low risk of bias. One study was at high risk of selection bias, attrition bias and other sources of bias. Risk of bias was unclear for the remaining studies across domains. We decided not to undertake a meta‐analysis because of variation in study design, types of interventions and outcome measurements. We present a narrative description of individual studies for each outcome.
All six studies assessed functional exercise capacity, although we noted wide variability in the nature of interventions, outcome measures and associated metrics and data reporting. Overall quality of the evidence was very low. Individually, three studies reported positive results in favour of the intervention. One study found a small short‐term benefit in anaerobic threshold (mean difference (MD) 1.8 mL O2/kg/min, 95% confidence interval (CI) 0.4 to 3.2; P value = 0.02). In a second study, both incremental (MD 4.7, 95% CI 1.69 to 7.75 watts; P value = 0.003) and endurance (MD 4.12, 95% CI 0.68 to 7.56 minutes; P value = 0.021) exercise testing results were improved with intervention. Finally self reported physical function increased significantly following use of a rehabilitation manual (P value = 0.006). Remaining studies found no effect of the intervention.
Similar variability was evident with regard to findings for the primary outcome of health‐related quality of life. Only two studies evaluated this outcome. Individually, neither study reported differences between intervention and control groups for health‐related quality of life due to the intervention. Overall quality of the evidence was very low.
Four studies reported rates of withdrawal, which ranged from 0% to 26.5% in control groups, and from 8.2% to 27.6% in intervention groups. The quality of evidence for the effect of the intervention on withdrawal was low. Very low‐quality evidence showed rates of adherence with the intervention. Mortality ranging from 0% to 18.8% was reported by all studies. The quality of evidence for the effect of the intervention on mortality was low. Loss to follow‐up, as reported in all studies, ranged from 0% to 14% in control groups, and from 0% to 12.5% in intervention groups, with low quality of evidence. Only one non‐mortality adverse event was reported across all participants in all studies (a minor musculoskeletal injury), and the quality of the evidence was low.
Authors' conclusions
At this time, we are unable to determine an overall effect on functional exercise capacity, or on health‐related quality of life, of an exercise‐based intervention initiated after ICU discharge for survivors of critical illness. Meta‐analysis of findings was not appropriate because the number of studies and the quantity of data were insufficient. Individual study findings were inconsistent. Some studies reported a beneficial effect of the intervention on functional exercise capacity, and others did not. No effect on health‐related quality of life was reported. Methodological rigour was lacking across several domains, influencing the quality of the evidence. Wide variability was noted in the characteristics of interventions, outcome measures and associated metrics and data reporting.
If further trials are identified, we may be able to determine the effects of exercise‐based intervention following ICU discharge on functional exercise capacity and health‐related quality of life among survivors of critical illness.
Guillain-Barré syndrome Willison, Hugh J, Prof; Jacobs, Bart C, Prof; van Doorn, Pieter A, Prof
The Lancet,
08/2016, Letnik:
388, Številka:
10045
Journal Article
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Summary Guillain-Barré syndrome is the most common and most severe acute paralytic neuropathy, with about 100 000 people developing the disorder every year worldwide. Under the umbrella term of ...Guillain-Barré syndrome are several recognisable variants with distinct clinical and pathological features. The severe, generalised manifestation of Guillain-Barré syndrome with respiratory failure affects 20–30% of cases. Treatment with intravenous immunoglobulin or plasma exchange is the optimal management approach, alongside supportive care. Understanding of the infectious triggers and immunological and pathological mechanisms has advanced substantially in the past 10 years, and is guiding clinical trials investigating new treatments. Investigators of large, worldwide, collaborative studies of the spectrum of Guillain-Barré syndrome are accruing data for clinical and biological databases to inform the development of outcome predictors and disease biomarkers. Such studies are transforming the clinical and scientific landscape of acute autoimmune neuropathies.
ICU-acquired weakness is thought to mediate physical impairments in survivors of critical illness, but few studies have investigated this thoroughly. The purpose was to investigate differences in ...post-ICU mortality and physical functioning between patients with and without ICU-acquired weakness at 6 months after ICU discharge.
ICU patients, mechanically ventilated ≥ 2 days, were included in a single-center prospective observational cohort study. ICU-acquired weakness was diagnosed when the average Medical Research Council score was <4 in awake and attentive patients. Post-ICU mortality was recorded until 6 months after ICU discharge; in surviving patients, physical functioning was assessed using the Short-Form Health Survey physical functioning domain. The independent effect of ICU-acquired weakness on post-ICU mortality was analyzed using a multivariable Cox proportional hazards model. The independent effect of ICU-acquired weakness on the physical functioning domain score was analyzed using a multivariable linear regression model.
Of the 156 patients included, 80 had ICU-acquired weakness. Twenty-three patients died in the ICU (20 with ICU-acquired weakness); during 6 months follow-up after ICU discharge another 25 patients died (17 with ICU-acquired weakness). Physical functioning domain scores were available for 96 survivors (39 patients with ICU-acquired weakness). ICU-acquired weakness was independently associated with an increase in post-ICU mortality (hazard ratio 3.6, 95% confidence interval, 1.3 to 9.8; P = 0.01) and with a decrease in physical functioning (β: -16.7 points; 95% confidence interval, -30.2 to -3.1; P = 0.02).
ICU-acquired weakness is independently associated with higher post-ICU mortality and with clinically relevant lower physical functioning in survivors at 6 months after ICU discharge.
•In polio survivors, gait pattern characteristics due to calf muscle weakness have not been fully described.•We examined gait pattern characteristics in association with underlying impairments.•We ...found 7 different gait patterns with two dominant patterns present.•Patients with a similar presentation of impairments did not necessarily walk alike.•The gait pattern could not be accurately predicted from underlying impairments.
The objective was to identify gait patterns in polio survivors with calf muscle weakness and associate them to underlying lower extremity impairments, which are expected to help in the search for an optimal orthosis.
Unilaterally affected patients underwent barefoot 3D-gait analyses. Gait pattern clusters were created based on the ankle and knee angle and ankle moment shown in midstance of the affected limb. Impairment clusters were created based on plantarflexor and knee-extensor strength, and ankle and knee joint range-of-motion. The association between gait patterns and underlying impairments were examined descriptively. The Random Forest Algorithm and regression analyses were used to predict gait patterns and parameters.
Seven gait patterns in 73 polio survivors were identified, with two dominant patterns: one with a mildly/non-deviant ankle angle, ankle moment and knee angle (n=23), and one with a strongly deviant ankle angle and a mildly/non-deviant ankle moment and knee angle (n=18). Gait pattern prediction from underlying impairments was 49% accurate with best prediction performance for the second dominant gait pattern (sensitivity 78% and positive predictive value 74%). The underlying impairments explained between 20 and 32% of the variance in individual gait parameters.
Polio survivors with calf muscle weakness who present a similar impairment profile do not necessarily walk the same. From physical examination alone, the gait pattern nor the individual gait parameters could be accurately predicted. The patient’s gait should therefore be measured to help in the prescription and evaluation of orthoses for these patients.
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